More evidence for a link between type 2 diabetes and Alzheimer’s

Glucose levels linked to cognitive decline in those with MCI

A study involving 264 older adults with mild cognitive impairment has found that those with normal glucose levels (167; 63%) had less cognitive decline over 2 years than those with impaired (high) glucose levels (97; 37%). They also showed less brain shrinkage and were less likely to develop Alzheimer’s. The fasting glucose levels were classified according to the American Diabetes criteria.

[3614] Vos SJB, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, Cairns NJ, Morris JC, Holtzman DM, Fagan AM. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. The Lancet Neurology [Internet]. 2013 ;12(10):957 - 965. Available from:

Rat study suggests cognitive decline in diabetics related to amyloid-beta buildup

A rat study supports the growing evidence of a link between type 2 diabetes and Alzheimer’s. In this study, 20 rats were fed a high-fat diet to give them type 2 diabetes. A subsequent test found that the diabetic rats had significantly poorer memories than the control group of rats on a healthy diet (the rats were taught to associate a dark cage with an electric shock; how long the rat continues to remember that the stimulus means a shock — as shown by their frozen reaction — is taken as a measure of how good their memory is; the diabetic rats froze for less than half the time of the controls).

The diabetic rats then had their brains (specifically, the hippocampus) injected with antibodies that disrupt amyloid-beta plaques. This produced no change in their behavior. However, when they were given antibodies that disrupt amyloid-beta oligomers (precursors of the plaques), the memory deficit was reversed, and they behaved the same as the healthy rats.

These findings suggest that the cognitive decline often seen in type 2 diabetes is not due to the disruption in insulin signaling, as thought, but rather the build-up of amyloid oligomers. Previous research has shown that the same enzymes break down both insulin and the oligomers, so when there’s a lot of insulin (which the enzymes prioritize), the enzymes don’t have as much opportunity to work on breaking down the oligomers. The oligomers collect, preventing the insulin from reaching their proper receptors in the hippocampus, which impairs cognitive function.

All this supports the idea that type 2 diabetes may be thought of as early-stage Alzheimer's. Obviously a lot more work needs to be done to confirm this picture, but certainly in the mean time, it can be taken as another reason to take type 2 diabetes very seriously.

McNay, E.C., Osborne, D., et al. 2014. Preliminary data presented at the Society for Neuroscience meeting in San Diego in November, 2013

High blood sugar makes Alzheimer’s plaque more toxic

A study of cell cultures taken from rodents’ cerebral blood vessels has found that, while cells exposed to either high glucose or amyloid-beta showed no changes in viability, exposure to both decreased cell viability by 40%. Moreover, cells from diabetic mice were more vulnerable to amyloid-beta, even at normal glucose levels.

The findings support evidence pointing to high glucose as a risk factor for vascular damage associated with Alzheimer’s, and adds weight to the view that controlling blood sugar levels is vital for those with diabetes.

[3558] Carvalho C, Katz PS, Dutta S, Katakam PVG, Moreira PI, Busija DW. Increased Susceptibility to Amyloid-β Toxicity in Rat Brain Microvascular Endothelial Cells under Hyperglycemic Conditions. Journal of Alzheimer's Disease [Internet]. 2014 ;38(1):75 - 83. Available from:

Mechanism by which diabetes increases Alzheimer's risk revealed

Although it's well-established now that diabetes is a major risk factor for dementia, the reason is still not well understood. To test the hypothesis that epigenetic changes in the brain, affecting synaptic function, may be part of the reason, the brains of diabetics and others were examined post-mortem. Diabetics' brains were found to have significantly higher expression of a class of molecules (histone deacetylases class IIa) and this was associated with impaired expression of synaptic proteins.

This finding was confirmed in mice genetically engineered to develop an Alzheimer’s-type condition, who were induced to develop diabetes. The increase of HDAC IIa was associated with synaptic impairments in the hippocampus, through the work of amyloid oligomers.

Some 60% of Alzheimer's patients have at least one serious medical condition associated with diabetes.

[3615] Wang J, Gong B, Zhao W, Tang C, Varghese M, Nguyen T, Bi W, Bilski A, Begum S, Vempati P, et al. Epigenetic Mechanisms Linking Diabetes and Synaptic Impairments. Diabetes [Internet]. 2014 ;63(2):645 - 654. Available from:

High Blood Sugar Linked to Dementia

A seven-year study involving 2,067 older adults (average age 76 at start) has found that those with a high blood glucose level, whether or not they had diabetes, were more likely to develop dementia. Moreover, this was a linear relationship — meaning that the risk steadily increased with higher glucose levels, and decreased the lower it was. Thus, even those with ‘normal’ glucose levels were subject to this relationship, with those whose blood sugar averaged 115 milligrams per deciliter, having an 18% higher risk of dementia than those at 100 mg/dL. Other risk factors, such as high blood pressure, smoking, exercise, and education, were taken into account in the analysis.

The findings add weight to the idea that the brain is a target organ for damage by high blood sugar.

Over the course of the study, a quarter (524) developed dementia of some kind, primarily Alzheimer’s disease or vascular dementia. At the beginning of the study, 232 (11%) had diabetes, and a further 111 developed it by the end of the study. Nearly a third (32%) of those with diabetes at the beginning of the study developed dementia, compared to just under a quarter of those without (24.5%).

The journal article is freely available at

[3563] Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, Haneuse S, Craft S, Montine TJ, Kahn SE, et al. Glucose Levels and Risk of Dementia. New England Journal of Medicine [Internet]. 2013 ;369(6):540 - 548. Available from:

Undiagnosed pre-diabetes highly prevalent in early Alzheimer's disease

A study involving 128 patients with mild to moderate Alzheimer’s disease, which had specifically excluded those with known diabetes, found that 13% of them did in fact have diabetes, and a further 30% showed glucose intolerance, a pre-diabetic condition.

Turner presented his findings at the Alzheimer's Association International Congress in Boston on July 14.

Association between hypoglycemia, dementia in older adults with diabetes

A 12-year study involving 783 older adults with diabetes (average age 74) has found that 148 (19%) developed dementia. Those 61 patients (8%) who had a reported hypoglycemic event were twice as likely to develop dementia compared to those who didn’t suffer such an event (34% vs. 17%). Similarly, those with dementia were more likely to experience a severe hypoglycemic event.

The findings suggest some patients risk entering a downward spiral in which hypoglycemia and cognitive impairment fuel one another, leading to worse health

[3622] Yaffe K, CM F, N H, et al. ASsociation between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Internal Medicine [Internet]. 2013 ;173(14):1300 - 1306. Available from:

Dementia risk greatest for older Native-Americans and African-Americans with diabetes

In the first study to look at racial and ethnic differences in dementia risk among older adults with type 2 diabetes, Native Americans were 64% more likely to develop dementia than Asian-Americans, and African-Americans were 44% more likely. Asian-Americans had the lowest risk, and non-Hispanic whites and Latinos were intermediate.

The study involved 22,171 older adults (60+), of whom 3,796 patients (17%) developed dementia over the 10 years of the study. Almost 20% of the African-Americans and Native Americans developed dementia.

The ethnic differences were not explained by diabetes-related complications, glycemic control or duration of diabetes, or neighborhood deprivation index, body mass index, or hypertension.

[3590] Mayeda ER, Karter AJ, Huang ES, Moffet HH, Haan MN, Whitmer RA. Racial/Ethnic Differences in Dementia Risk Among Older Type 2 Diabetic Patients: The Diabetes and Aging Study. Diabetes Care [Internet]. 2014 ;37(4):1009 - 1015. Available from:

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